6,532 research outputs found
Thrombolysis and thrombectomy for acute ischaemic stroke
The likelihood of disability-free recovery after acute ischemic stroke is significantly improved by reperfusion either by intravenous thrombolytic drug treatment or with endovascular mechanical thrombectomy in selected cases. The use of intravenous thrombolysis is limited by the short treatment window and you need to assess individual balance of benefit and risk of symptomatic intracranial haemorrhage. Benefit is greater for shorter onset-to-reperfusion time intervals, requiring optimisation of pre-hospital and in-hospital pathways. Symptomatic haemorrhage is more likely with more severe strokes, but a greater proportion of patients are left free of disability than suffer a treatment-related haemorrhage at all levels of severity. Extracranial haemorrhage and orolingual angioedema are less common complications. Endovascular mechanical thrombectomy can be used in selected patients with imaging-proven large artery occlusion. Successful therapy depends on well-organised services that can deliver treatment within a short time window at centres with adequate expertise to perform the procedure
Neuroimaging as a selection tool and endpoint in preclinical and clinical trials
Standard imaging in acute stroke enables the exclusion of non-stroke structural CNS lesions and cerebral haemorrhage from clinical and pre-clinical ischaemic stroke trials. In this review, the potential benefit of imaging (e.g., angiography and penumbral imaging) as a translational tool for trial recruitment and the use of imaging endpoints are discussed for both clinical and pre-clinical stroke research. The addition of advanced imaging to identify a “responder” population leads to reduced sample size for any given effect size in phase 2 trials and is a potentially cost-efficient means of testing interventions. In pre-clinical studies, technical failures (failed or incomplete vessel occlusion, cerebral haemorrhage) can be excluded early and continuous multimodal imaging of the animal from stroke onset is feasible. Pre- and post-intervention repeat scans provide real time assessment of the intervention over the first 4–6 h. Negative aspects of advanced imaging in animal studies include increased time under general anaesthesia, and, as in clinical studies, a delay in starting the intervention. In clinical phase 3 trial designs, the negative aspects of advanced imaging in patient selection include higher exclusion rates, slower recruitment, overestimated effect size and longer acquisition times. Imaging may identify biological effects with smaller sample size and at earlier time points, compared to standard clinical assessments, and can be adjusted for baseline parameters. Mechanistic insights can be obtained. Pre-clinically, multimodal imaging can non-invasively generate data on a range of parameters, allowing the animal to be recovered for subsequent behavioural testing and/or the brain taken for further molecular or histological analysis
Scarlet Phosphorus: A New Chemically Active Variety of Red Phosphorus, and Its Use in the Manufacture of Matches
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Stroke in the acute setting
Acute stroke and transient ischaemic attack (TIA) are focal neurological syndromes of vascular origin and should be treated as medical emergencies. Brain imaging with computed tomography or magnetic resonance imaging is required to distinguish ischaemic stroke from intracerebral haemorrhage, recognize non-stroke pathologies that mimic stroke and guide investigation into the underlying mechanism. Acute interventions of benefit in ischaemic stroke include intravenous thrombolysis with alteplase given within 4.5 hours of onset, endovascular thrombectomy within 6 hours of onset in selected patients, stroke unit care and aspirin. Decompressive hemicraniectomy reduces mortality in ischaemic stroke complicated by severe brain swelling. Intracerebral haemorrhage accounts for 10–15% of strokes, and while specific treatments are lacking at present, patients benefit from general measures, notably stroke unit care. TIA carries a high short-term risk of stroke, and immediate investigation and institution of secondary preventive treatment prevents a high proportion of this. Secondary prevention for ischaemic stroke and TIA should be tailored according to mechanism in individual patients
Crystal Structure Analyses of Organic and Organometallic Compounds
The thesis is divided into three parts: the first part is a brief review of the theory and methods of x-ray crystallography, the second part describes a number of computer programmes devised either wholly or partly by the author, and in the third part accounts of three structure analyses are presented. The computer programmes described in Part II are written in ALGOL for the English Electric KDP9 Computer. The molecular functions system is a group of six programmes for interpreting the results of a structure analysis: bond lengths and interbond angles with their standard deviations, intermolecular contacts, and mean plane equations may be calculated and rigid-body vibrational analysis can be carried out. The automatic structure solution (ASS) system allows semi-automatic Fourier refinement to be performed. The minimum residual programme permits crystal structures to be refined in projection by direct calculation of the minimum R-factor. The structure analyses presented in Part III are applications of the x-ray method to organic and organo-metallic structural problems. It has been known for more than twenty years that indene can form a 1:2 adduct with dimethylacetylene-dicarboxylate. Earlier chemical and spectroscopic studies on the adduct did not lead to a successful structure determination. The molecular structure of the adduct has now been definitely established by x-ray analysis of its dibromo-derivative. The structure analyses of phenanthrenechromium tricarbonyl, C14H10Cr(CO)3, and of 9,10-dihydrophenanthrenechromium tricarbonyl, C14H12Cr(CO)3, were undertaken to obtain accurate dimensions for aromatic rings bonded to chromium. In both analyses the standard deviations of the C-C bonds range from 0.006 to 0.010 A. The results suggest that the chromium atom causes a slight increase in the mean bond length of the bonded ring without alteration of the ring symmetry. Structural studies on related arenechromium complexes are discussed
Clinical trial design for stem cell therapies in stroke: What have we learned?
Stem cells of various sources have been investigated in a series of small, safety and feasibility-focused studies over the past 15 years. Understanding of mechanisms of action has evolved and the trial paradigms have become focused on two different approaches – one being an early subacute delivery of cells to reduce acute tissue injury and modify the tissue environment in a direction favourable to reparative processes (for example by being anti-inflammatory, anti-apoptotic, and encouraging endogenous stem cell mobilisation); the other exploring later delivery of cells during the recovery phase after stroke to modulate the local environment in favour of angiogenesis and neurogenesis. The former approach has generally investigated intravenous or intra-arterial delivery of cells with an expected paracrine mode of action and no expected engraftment within the brain. The latter has explored direct intracerebral implantation adjacent to the infarct. Several relevant trials have been conducted, including two controlled trials of intravenously delivered bone marrow-derived cells in the early subacute stage, and two small single-arm phase 1 trials of intracerebrally implanted cells. The findings of these studies and their implications for future trial design are considered
Recommendations for Heartworm Therapy and Canine GDV: Heart Rhythm Disturbances
In recent months, several articles have appeared in lay magazines espousing the use of new drugs for heartworm prevention and treatment. Because of the popularity of these magazines and the so-called infallibility of the printed word, you may be asked to answer numerous questions on this subject from your clientele.
Gastric Dilation Volvulus (GDV), otherwise known as bloat, is a critical and often fatal disease affecting dogs. A great deal of information relating to age, sex, breed, signs and symptoms associated with bloat in dogs has been obtained from clinical observations
Developing Christ as Consolatory Example in the Christ Encomium
While Paul Holloway’s scholarship on Philippians has been important, his classification of Philippians as a letter of consolation has gained relatively little traction. Interestingly, however, Holloway follows Karl Barth in labelling a large section of the letter, Phil 1:27–2:16, a ‘hortatory digression’, which could be seen to diminish the extent of consolation in this part of the letter. In this article, I seek to develop Holloway’s work to argue that the Christ encomium in Phil 2:6–11 has elements of consolatory discourse that relates to other parts of the letter. Phil 2:6–11 illustrates and exemplifies how comfort (παράκλησις), consolation (παραμύθιον), and joy (χαρά) can be derived by individuals and communities in the face of opposition or destitution (cf. Phil 1:27–2:4). I propose that Christ undergoes a form of voluntary desolation in 2:6–8 but then receives something different from consolation in his glorious exaltation and the bestowal of the divine name. Although Paul and the Philippians will not receive universal worship like Christ, they can imitate him by following in this trajectory of becoming like God, thus receiving divine consolation and transformation
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